Drosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes was written by Chi, Wanhao;Iyengar, Atulya S. R.;Fu, Wenqin;Liu, Wei;Berg, Abigayle E.;Wu, Chun-Fang;Zhuang, Xiaoxi. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2022.SDS of cas: 54-47-7 The following contents are mentioned in the article:
Pyridox(am)ine 5′-phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5′-phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in PNPO have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities. Recently, the PNPO gene has also been implicated in epilepsy in adults. It is unclear how these phenotypic variations are linked to specific PNPO alleles and to what degree diet can modify their expression. Using CRISPR-Cas9, we generated four knock-in Drosophila alleles, hWT, hR116Q, hD33V, and hR95H, in which the endogenous Drosophila PNPO was replaced by wild-type human PNPO complementary DNA (cDNA) and three epilepsy-associated variants. We found that these knock-in flies exhibited a wide range of phenotypes, including developmental impairments, abnormal locomotor activities, spontaneous seizures, and shortened life span. These phenotypes are allele dependent, varying with the known biochem. severity of these mutations and our characterized mol. defects. We also showed that diet treatments further diversified the phenotypes among alleles, and PLP supplementation at larval and adult stages prevented developmental impairments and seizures in adult flies, resp. Furthermore, we found that hR95H had a significant dominant-neg. effect, rendering heterozygous flies susceptible to seizures and premature death. Together, these results provide biol. bases for the various phenotypes resulting from multifunction of PNPO, specific mol. and/or genetic properties of each PNPO variant, and differential allele-diet interactions. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7SDS of cas: 54-47-7).
(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.SDS of cas: 54-47-7